Regulation of nitric oxide production in response to skeletal muscle activation

Nitric oxide (NO) is synthesized in normal muscle fibers by the neuronal (n NOS) and the endothelial (ecNOS) isoforms of nitric oxide synthase (NOS). N O contributes to the regulation of several processes such as excitation-con traction coupling and mitochondrial respiration. We assessed in this study whether NO production is regulated in response to an acute increase in musc le activation. Three groups of anesthetized, tracheostomized, spontaneously breathing rats were examined after an experimental period of 3 h. Group 1 served as a control (no loading), whereas groups 2 and 3 were exposed to mo derate and severe inspiratory resistive loads, respectively, which elicited tracheal pressures of 30 and 70% of maximum, respectively. Ventilatory (di aphragm, intercostal, and transverse abdominis) and limb (gastrocnemius) mu scles were excised at the end of the experimental period and examined for N OS activity and NOS protein expression. Neither submaximal nor maximum trac heal pressures were altered after 3 h of resistive loading. Diaphragmatic a nd intercostal muscle NOS activities declined significantly in response to moderate and severe loading, whereas those of transverse abdominis and gast rocnemius muscles remained unchanged. On the other hand, resistive loading had no significant effect on ventilatory and limb muscle NOS isoform expres sion. We propose that a contraction-induced decline in muscle NOS activity represents a compensatory mechanism through which muscle contractility and mitochondrial function are protected from the inhibitory influence of NO.